Worms, Life and Death: Cell Suicide in Development and Disease

Description: A microscopic roundworm has come to play a dominant role in some of the most pivotal medical research of our time. In the labs of Robert Horvitz and his colleagues, C. elegans has helped reveal cell death as a normal part of biological development.
In this talk, Horvitz painstakingly delineates the series of discoveries based on C. elegans that identified the genetics behind programmed cell death (apoptosis), the disorders that emerge if this normal process stalls, and human counterparts to these disorders, which suggest potential targets for therapy.
Because the mature roundworm consists of just 959 cells, it was possible for scientists to track the organism's entire lineage of cell divisions, and to characterize what genetic accidents created mutant worms.
Scientists figured out genetic pathways that were essential to normal development in the worm, and which, if disrupted, led to harmful mutations. For instance, the immature roundworm contains 131 cells that are not found in the adult, because they are genetically programmed to die. Every animal, Horwitz says, undergoes apoptosis as a -normal aspect of development." Tadpoles lose their tails to become frogs; lots of animals have webbing -sculpted out by the process of programmed cell death." Over years, Horvitz and his colleagues determined the precise genes responsible for programmed cell death in C. elegans, as well as the genes that protect cells from dying, and the way these genes interact. Horvitz's teams also found likely human equivalents to these critical genes and pathways. If these genes go awry, says Horvitz, -then something is going to lead to disease."
Cancer, autoimmune diseases and viral infections result from too little programmed cell death. That's because cell division goes unchecked. There are also human diseases that occur because cells die when they should not: neurodegenerative disorders, retinal degeneration, liver disease, and heart attacks. As a result of Horvitz's work, many new targets have emerged for these diseases, some of which Horvitz himself is pursuing. Horvitz is now aiming his sights at different genetic regulators that tell certain types of cells to live or die, leading to novel therapies for some of our most formidable diseases.

About the Speaker(s): H. Robert Horvitz won the 2002 Nobel Prize in Physiology or Medicine (with Sydney Brenner and John Sulston), for his work on programmed cell death (apoptosis), and for his studies concerning organ development in C. elegans. His apoptosis studies may also improve the understanding of neurological disorders such as amyotrophic lateral sclerosis (ALS), a disease that killed Horvitz's father in 1989. In collaboration with others, Horvitz identified a gene involved in the inherited form of ALS, and he is also pursuing other genes involved in the disease. "My hope is that my discoveries will one day lead to advances in medicine that alleviate human suffering and contribute to the world in ways that will benefit mankind," Horvitz has said.

He is also an investigator for the Howard Hughes Medical Institute and a member of the McGovern Institute for Brain Research at MIT, and a member of the MIT Center for Cancer Research. He holds appointments at the Massachusetts General Hospital in neurology and in medicine.

Horvitz received bachelor's degrees in mathematics and economics from MIT (1968) and an M.A. and Ph.D. (1974) in biology from Harvard University. He was a postdoctoral researcher at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. He joined the faculty of MIT in 1978 and became professor of biology in 1986 and an investigator of the Howard Hughes Medical Institute in 1988.